The main goal of this Mentored Patient-Oriented Career Development Award is to study the role of subclinical cardiovascular (CV) factors in the decline in cognitive function, in subjects with known mild cognitive impairment. This Award will allow Dr. Marenberg to achieve this goal by expanding upon her prior research training in epidemiology and geriatrics and developing additional expertise in the fields of both dementia research and subclinical vascular measurement. Dr. Marenberg plans to achieve these goals educationally by participating in both the Alzheimer's Disease Center's Memory Disorders Clinic and the Preventive Cardiology Clinic at the University of Pennsylvania, under the guidance of her mentors, Dr. Daniel Rader and Dr. Chris Clark. She will take didactic coursework in the cognitive neurosciences, as well as present her research in seminars at the Center for Neurodegenerative Research, the Institute on Aging, and the Center for Clinical Epidemiology and Biostatistics, where her co-sponsor, Dr. Jeane Anne Grisso has an appointment. Dr. Marenberg will also achieve these objectives by developing and implementing her research protocol. Research Plan: There is growing evidence for the role of cardiovascular disease and its risk factors in dementia clinically diagnosed as Alzheimer's disease. Understanding the role of subclinical vascular factors in cognitive function may best be studied in individuals who are at high risk of developing dementia, i.e., those with mild cognitive impairment. The subclinical CV measure of coronary calcification has never been evaluated in relation to cognitive function. The specific aims of the proposed study, therefore, are 1 ) to identify whether traditional cardiovascular risk factors predict progression of mild cognitive impairment over time; 2) to determine whether traditional serum based cardiovascular risk factors (high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides) and new cardiovascular risk factors (lipoprotein (a) [Lp(a)], homocysteine, hyperinsulinemia, and fibrinogen), predict progression of mild cognitive impairment over time; and 3) to investigate whether subclinical non-invasive anatomic measures of atherosclerosis, such as coronary calcification and carotid intima media thickness, as well as changes in these measures, predict progression of mild cognitive impairment over time.